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Scientists in WSU’s College of Veterinary Medicine and College of Pharmacy and Pharmaceuticals Sciences (CPPS) have discovered an important step in the progression of the body’s inflammatory response that may soon lead to effective management and treatments.
“Inflammation is vital for life, without it you will die,” said Professor Santanu Bose with WSU’s Department of Veterinary Microbiology and Pathology. “But inflammation can also debilitate or kill the very organism it is trying to save. Diabetes, Alzheimer’s disease, atherosclerosis, arthritis, cancer, pneumonia, and other infections are all examples where even after the benefits of inflammation have been attained, it is the continued, seemingly uncontrolled inflammation that makes things much worse, even deadly.”

The collaborative team effort was led by Dr. Bose along with Assistant Professor Senthil Natesan in CPPS, and the former director of WSU’s School of Molecular Biosciences, Professor Jonathan Jones. In all, 11 scientists’ work led to the discovery of a naturally-occurring modified form of cholesterol that binds to key cell surface proteins called integrins. Once bound, the complex acts to signal surrounding cells at the site of an infection or during metabolic insult to induce inflammation.
Dr. Bose explained, “What we found was that when a white blood cell called a macrophage encounters a foreign organism, say a virus, a gene in the cell turns on and produces a type of cholesterol,” . “In our case we used an influenza A virus and respiratory syncytial virus as our models. This cholesterol then converts into another form of the lipid named 25-hydroxycholesterol or 25HC for short.

Assistant Professor Senthil Natesan said “Once produced, 25HC then leaves the cell and encounters other nearby macrophages where a receptor protein on the surface called an integrin is waiting, sort of like an antenna that waits to receive a radio signal. Once 25HC binds to the integrin it amplifies the inflammatory response. “This is the first time scientists have found a lipid acting in this manner to amplify inflammation.”

“Integrin receptors are key regulators ensuring cells and tissues function normally,” said Jones. “Identification of this pathway provides a better understanding of how lipids affect integrin functions in both normal and diseased tissues. Our data might also explain why taking anti-cholesterol medications like statins actually decrease certain cancer risks since they inhibit integrins.”
Currently, the team is working closely with WSU’s Office of Commercialization to develop anti-25HC based anti-inflammatory therapeutic agents to combat various inflammatory diseases.

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